Fibromyalgia is characterized by symptoms of widespread pain and increased sensitivity to painful and non-painful sensory stimulation. The pattern of sensory modality sensitivity varies across individuals. This variance may be due to the contribution of non-sensory factors, especially the unpleasant affective components that motivate behaviors of escape and avoidance. The relative contribution of these elements to altered sensory processing of painful and non-painful stimuli is not known and may account for the limited characterization of the underlying mechanisms of fibromyalgia. The proposed work will identify the role of mechanisms mediating feelings of distress and discomfort in patients with fibromyalgia. The methods use psychophysical multi-method techniques (aim 1), behavioral measures of discrimination performance and aversiveness (aim 2), and functional neuro-imagining (aim 3) to characterize common mechanisms of intensity and affective processing in fibromyalgia and healthy controls, and to characterize the role of brain processing regions implicated in sensory discriminative (primary and secondary somatosensory cortex) and affective (insular and anterior cingulate cortex) processing. The specific psychophysical procedures reduce spurious correlations between intensity and unpleasantness responses. These procedures and behavioral evaluation of discrimination performance and relative and absolute aversiveness will determine the contributions of increased sensory gain and central affective gain in two nociceptive (heat, pressure) and one non-nociceptive stimulus modality (audition) to the symptoms of fibromyalgia and compares these to responses from healthy control subjects. Fibromyalgia is a significant health and economic problem mediated by unknown mechanisms. Current treatments are only marginally effective. Once the mechanisms that initiate and maintain fibromyalgia are understood, this knowledge can be applied to the development of effective rational treatments. We expect that the proposed investigation of altered sensory processing will uncover important information that will significantly advance understanding of the underlying mechanisms. Such an advance is significant since it will guide further investigations of treatments. We expect these results to apply to multiple diagnostic categories and greatly increase the understanding and treatment fibromyalgia and related disorders. PROJECT NARRATIVE: This research will improve the understanding of the underlying mechanisms of fibromyalgia. A better understanding of mechanisms and pain processes will lead to improved therapies and better detection of who will respond to certain types of therapies. The outcomes of this study will also provide better information about phenotypic characteristics that will be useful in guiding future genetic studies.